DESCRIPTION: A normal long-lived, dark-eyes mouse strain, the (C57BL/6xDBA/2) F1 hybrid mouse has been studied for late life incidence of cataracts. This incidence approaches 100% in very late life and, in preliminary studies, appears to accumulate progressively during old age in mice. The time of cataract occurrence and its non-association with other eye or general systemic pathologies differentiate this mouse model from others now in use. These particulars indicate that it promises to be an ideal model for the human aging cataract. It is the intent of the applicants to complete the model studies involving time of occurrence, the genetic background involved, the histopathology of the lens and adjoining eyes, and the possible importance of oxidative DNA damage in its causation. It will be determined whether this mouse strain is unique in its very high late incidence of cataracts or whether other strains will provide similar findings. Of particular importance is the fact that life long caloric restriction (CR) at 60% of ad libitum (AL) diet significantly reduces the incidence and delays the appearance of the cataracts. CR has been shown to reduce oxidative damage to cells and their DNA and to preserve the replicative capacity of cells both in vivo and in vitro. The amount of DNA damage present, measured as either or single or double stranded DNA breaks, as well as telomeric shortening, will be determined in the lens epithelial cells of chronologically spaced groups of mice. This will be done both in untreated lens cells and in those that have received an in vitro oxidative challenge. Any effects of lifetime light exposure will be accounted for. All of these measurements will be matched to the ability of the lens cells from the same donors to form large clones in culture, a reliable measurement of physiological cellular aging. This study will define a mouse model for human age-related cataract formation and will use it to provide information on the harmful role of oxidative damage to lens epithelial cell DNA, correlating this with cataract development.